Inhibitory effects of guava (Psidium guajava L.) leaf extracts and its active compounds on the glycation process of protein

Hyperglycaemia causes increased protein glycation and the formation of early glycation products and advanced glycation end products (AGEs) which are major factors responsible for the complications of diabetes. This study investigated the ability of guava leaf and compounds to inhibit glycation process in an albumin/glucose model system and compared the potency of these extracts with Polyphenon 60 which is a commercial polyphenol product extracted from green tea and with the standard antiglycation agent, aminoguanidine. The results showed that the inhibitory effects of guava leaf extracts on the formation of α-dicarbonyl compounds were over 95% at 50 μg/ml. Phenolic compounds present, namely gallic acid, catechin and quercetin exhibited over 80% inhibitory effects, but ferulic acid showed no activity. The guava leaf extracts also showed strong inhibitory effects on the production of Amadori products and AGEs from albumin in the presence of glucose. The phenolic compounds also showed strong inhibitory effects on the glycation of albumin, especially quercetin exhibited over 95% inhibitory effects at 100 μg/ml. According to the results obtained, guava leaf extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes.     

Advanced glycation end products inhibitors from Alpinia zerumbet rhizomes

Advanced glycation end products (AGEs) are major factors responsible for the complication of diabetes. The present study was carried out to investigate the inhibitory activities on fructosamine adduct and α-dicarbonyl formations by hexane extracts of various parts of Alpinia zerumbet. Furthermore, we isolated two previously known compounds, namely 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK). 8(17),12-Labdadiene-15,16-dial (labdadiene) was isolated for the first time from the rhizome of A. zerumbet. The results showed that labdadiene (IC₅₀ = 51.06 μg/mL) had similar activity to rutin and quercetin against fructosamine adduct. The inhibition of α-dicarbonyl compounds formation by labdadiene was significantly higher than that of DK and DDK. Our results indicate that labdadiene is a potent antiglycation agent which was found to inhibit AGEs formation in three different steps in the pathway. These data indicate that labdadiene could be used to prevent glycation-associated complications in diabetes.     

Antiglycative and antioxidative properties of coffee fractions

In this work the inhibitory activity of coffee low molecular weight compound (LMWC) and high molecular weight compound (HMWC) fractions against in vitro advanced glycation end-products (AGEs) formation was investigated. The HMWC fraction was characterised for its content in total phenolic groups, proteins and carbohydrates. The chlorogenic acids of LMWC fraction were identified by liquid chromatography coupled with tandem mass spectrometry. HMWC inhibited bovine serum albumin glycation by acting as radical scavenger and Fe-chelator in the post-Amadori phase of the reaction and by inhibiting dicarbonyl reactive compounds production during glucose autoxidation. LMWC fraction was able to inhibit protein glycation and dicarbonyl reactive compounds formation more than HMWC fraction. Chlorogenic acids are the main compounds responsible for the antiglycative activity of LMWC fraction.     

槲皮素与葛根素对食品体系中非酶糖基化的抑制作用

通过对果糖胺、二羰基化合物、5-羟甲基糠醛（5-hydroxymethylfurfural,5-HMF）和荧光性末端产物的检测,考察槲皮素和葛根素对食品体系非酶糖基化反应的抑制作用。结果表明：槲皮素能促进非酶糖基化早期产物果糖胺和5-HMF的生成,对反应中期的二羰基化合物和非酶糖基化末端产物（advanced glycation end products,AGEs）具有较强的抑制作用;葛根素能促进果糖胺的生成,抑制二羰基化合物的生成,对5-HMF和AGEs无影响。这可能与槲皮素与葛根素的结构差异有关。     

8种别样茶对AGEs抑制能力的筛选及其抑制机制探究

目的:本研究通过检测非酶糖基化终末产物（advanced glycation end-products,AGEs）生成量评价8种别样茶的糖基化抑制能力,并探究抑制效果较好的别样茶对AGEs生成各阶段的抑制作用机制。方法:本研究首先对8种别样茶水提液中总黄酮含量进行检测,接着通过构建体外蛋白质非酶糖基化模型实验检测了8种别样茶抑制AGEs生成的能力,最后择优测定其对糖基化早期产物果糖胺、中期产物活性羰基化合物以及蛋白质交联的抑制能力,从而探究其对非酶糖基化反应的抑制机制。结果:大叶苦丁茶（Ilex latifolia Thunb）和甜茶（Rubus suavissimus S. Lee）对AGEs的抑制效果在8种别样茶中较为突出,50 μg/mL时AGEs抑制率分别达到了76.31%±0.87%和81.75%±0.41%;大叶苦丁茶和甜茶主要通过抑制糖基化早期、中期产物的生成量来减少AGEs的产生。其中,500 μg/mL甜茶对果糖胺抑制率最高（59.12%）,蛋白质交联抑制率最高（81.41%）,5000 μg/mL大叶苦丁茶对活性羰基化合物抑制率最高（94.24%）。结论:大叶苦丁茶及甜茶可以作为抑制糖基化反应的功能食品,本研究可为具有抑制AGEs产生功效原料的综合开发利用提供一定的理论依据。     

Antioxidation and antiglycation of 95% ethanolic extracts prepared from the leaves of black nightshade (Solanum nigrum)

Hyperglycemia results in the formation of advanced glycation end-products (AGE), resulting in an inflammatory response that induces insulin resistance. Evidence indicates that antioxidants can suppress the formation of reactive oxygen species, decrease levels of AGEs by inhibiting glycation. Black nightshade (Solanum nigrum) can be used as a medicinal food for improving blood glucose; however, the identities of the active compounds and how they counteract diabetes remain unknown. This study demonstrate that 95% ethanolic extracts of black nightshade exerted significant antioxidative activity compared with 50% ethanolic extracts and aqueous extracts. Moreover, 95% ethanolic extracts of black nightshade produced antiglycative activity, which contributed to the inhibition of fructosamine and generation of α-dicarbonyl compounds. The concentrations of solasonine and solamargine in the 95% ethanolic extracts were 0.484 and 0.183 mg/mg, respectively. These results suggest that black nightshade might serve as a novel source of functional ingredients that exert antiglycation and anti-diabetes activities.     

Anti-glycation and inhibition of starch hydrolyzing enzymes by enzymatically hydrolysed djulis (Chenopodium formosanum Koidz.) hull,leaf and seedling

Glycation is the reaction of the carbonyl group of the reducing sugars to form advanced glycation end products (AGEs), which are major contributors to glycation-related diabetes. Hence, it is necessary to find an alternative approach in management of diabetes that can reduce the formation of AGEs. Therefore, we investigated the anti-glycation and starch hydrolysing enzymes inhibition by djulis (Chenopodium formosanum Koidz.) hull, leaf and seedling treated with enzymatic hydrolysis (EH) and studied the possible phenolic compounds responsible for the anti-glycation efficacy. Djulis samples treated with EH showed a high inhibitory effect on AGEs (65.04–72.77%), methylglyoxal (80.01–90.70%), α-amylase (86.37–93.50%) and α-glucosidase (35.50–38.16%). Bioactive compounds were significantly contributed to the anti-glycation potential of djulis samples. Therefore, djulis hull, leaf and seedling treated with EH could be used as a natural potential source in the prevention of glycation-associated diabetes, health risks and to increase food productivity.     

槲皮素抑制蛋白糖基化及DNA损伤

建立牛血清白蛋白（bovine serum albumin,BSA）-还原糖、牛血清白蛋白-甲基乙二醛/乙二醛（bovineserum albumin-methylglyoxal/glyoxal,BSA-MGO/GO）反应体系,研究槲皮素对反应体系中晚期糖基化终产物（advanced glycation endproducts,AGEs）的抑制作用。考察了槲皮素在不同阶段对BSA-核糖体系中AGEs形成的抑制作用。并对槲皮素抑制二羰基化合物对质粒pBR322DNA的损伤进行研究。结果表明：槲皮素具有抑制BSA-还原糖、BSA-GO、BSA-MGO体系中AGEs形成的作用,达到显著抑制效果的浓度分别为1、0.25、0.25 mmol/L。槲皮素对BSA-MGO体系中AGEs产生的抑制作用强于BSA-GO体系。在BSA-核糖体系中,反应初期随着反应时间的延长抑制作用不断增大,12 d后,抑制作用趋于平缓,维持在60%左右。槲皮素对二羰基化合物对DNA的损伤有抑制作用,且与浓度成一定相关性。     

色氨酸抑制体外模型中晚期糖基化终末产物形成机理

食源性晚期糖基化终末产物(advanced glycation end products,AGEs)与多种慢性疾病密切相关,尤其是糖尿病和肾脏疾病.为减少AGEs对机体的健康风险,降低食品中AGEs含量,本研究从13种氨基酸中筛选出具有良好AGEs抑制效果的色氨酸(tryptophan,Trp),利用牛血清白蛋白(bo...     

芦蒿秸秆黄酮类化合物对晚期蛋白质糖基化终末产物形成的抑制作用

通过建立牛血清白蛋白-丙酮醛（bovine serum albumin-methylglyoxal,BSA-MGO）的蛋白质糖基化反应模型,用荧光法测定体外晚期蛋白质糖基化终末产物（advanced glycation end products,AGEs）的含量,探讨芦蒿秸秆黄酮类化合物对AGEs形成的抑制效果,并对木犀草素的作用途径进行探索。结果表明：芦蒿秸秆总黄酮浸膏经AB-8树脂分离后共收集到4 组含有黄酮的洗脱组分（F-10、F-30、F-50、F-70）对AGEs的形成均具有抑制作用,抑制效果由强到弱为依次为F-50＞F-30＞F-10＞F-70,此结果与F-30和F-50分离纯化得到的黄酮成分芦丁和木犀草素具有较好的AGEs抑制效果相一致。同时发现,芦蒿秸秆对AGEs形成的抑制效果与总黄酮含量存在显著的线性关系。另外,将木犀草素与MGO的反应产物进行分离纯化,高效液相色谱-质谱联用分析显示：木犀草素作用途径为通过捕获MGO,形成木犀草素-MGO加和物来抑制AGEs的形成。芦蒿秸秆黄酮类化合物可抑制体外蛋白质糖基化反应的活性预示其可以作为AGEs的天然抑制剂来预防和减轻糖尿病及其并发症。     

Inhibitory effects of Lemon balm (Melissa officinalis, L.) extract on the formation of advanced glycation end products

Lemon balm (Melissa officinalis) is a medicinal herb possessing functional compounds with unexplored anti-glycative action. The anti-glycative activity of Lemon balm extract was evaluated in the bovine serum albumin (BSA)/glucose system. The level of glycation, conformational alterations and protein binding to RAGE receptors were assessed by specific fluorescence, Congo red binding assay, circular dichroism, ligand and Western blotting. Ethanol fractions of Melissa leaf exhibited the highest inhibitory effects on the formation of advanced glycation end products (AGEs) and the late stage of glycation process. Significant alteration in the secondary structure of albumin was observed upon glycation, which was mitigated by applying the herb extract. Moreover, upon treatment with balm extract, glycated albumin adopts a secondary structure impeding its detection by RAGE receptors of microglial cells. Our results represent the anti-glycative properties of Melissa extract and its application for possible treatment of AGE-associated diseases.     

Inhibitory effects of microalgal extracts on the formation of advanced glycation endproducts (AGEs)

The antiglycative activities of 20 microalgae at different growth phases were evaluated for the first time. In a bovine serum albumin (BSA)-glucose system, ethyl acetate fractions of green microalgae Chlorella and diatom Nitzschia laevis exhibited the highest inhibitory effects against the formation of total advanced glycation endproducts (AGEs) (inhibition rates: 81.76–88.02% and 91.68%) at the concentration of 500 ppm. Such abilities were higher than the effect of 1 mM aminoguanidine (AG) solution (inhibition rate: 80.51%), a commonly used inhibitor of glycation process. In addition to total AGEs, these fractions were also found to be effective in the blockage of the formation of two specific AGEs, pentosidine and N^ε-Carboxymethyllysine (CML). Different from many other plant species, AGE inhibitory abilities of selected microalgae were not due to the presence of phenolic compounds. HPLC and gas chromatography (GC) analysis revealed that carotenoids in Chlorella and unsaturated fatty acids, mainly of linoleic acid, arachidonic acid and eicosapentaenoic acid in Nitzschia laevis contributed to their strong antiglycative capacities.     

Inhibitory effect of mung bean extract and its constituents vitexin and isovitexin on the formation of advanced glycation endproducts

The anti-glycation activity of four kinds of beans including mung bean, black bean, soybean and cowpea were evaluated. Aqueous alcohol extract of mung bean exhibited the strongest inhibitory activity against the formation of fluorescent advanced glycation endproducts (AGEs) in a bovine serum albumin (BSA)-glucose model, and the inhibitory activities of extracts of the four beans were found to be highly correlated with their total phenolic contents (R² = 0.95). Subsequent HPLC analysis of mung bean extract revealed two major phenolics which were purified and identified as vitexin and isovitexin by spectral methods. In the anti-glycation assays, both vitexin and isovitexin showed significant inhibitory activities against the formation of AGEs induced by glucose or methylglyoxal with efficacies of over 85% at 100 μM. In another assay, vitexin and isovitexin failed to directly trap reactive carbonyl species, such as methylglyoxal, suggesting that their anti-glycation activities may mainly be due to their free radical scavenging capacity.     

桑椹花色苷对晚期糖基化末端产物抑制作用及其机制分析

晚期糖基化末端产物(Advanced Glycation End Products,AGEs)是蛋白质游离氨基与还原糖羰基反应形成的一类复杂物质的总称,是诱发糖尿病等多种慢性病的重要因素之一,而多酚类化合物能够抑制AGEs的形成。为了探讨桑椹花色苷对AGEs的抑制机制,建立牛血清蛋白(BSA)/葡萄糖(Glucose)生成AGEs模拟反应体系,以0.5%酸性乙醇提取、AB-8型大孔树脂纯化的桑椹花色苷为抑制剂,测定反应体系中蛋白质羰基、巯基含量变化、羟基自由基(·OH)对AGEs形成的影响,利用SDS-PAGE凝胶电泳技术分析BSA的分子量变化。研究结果表明,随着桑椹花色苷浓度的增加,反应体系中的AGEs含量显著降低(P0.05)。桑椹花色苷可显著抑制·OH诱导的AGEs的形成(P0.05)。桑椹花色苷通过保护巯基和抑制蛋白质形成羰基而抑制AGEs生成;SDS-PAGE图谱显示,桑椹花色苷可阻断糖基化反应导致的蛋白质交联物的形成。     

Anti-melanogenesis properties of quercetin- and its derivative-rich extract from Allium cepa

In an effort to find a new whitening agent, we have found that the methanol extract of the dried skin of Allium cepa showed inhibition of melanin formation. Bioassay-guided fractionation led to the isolation of quercetin (1) and quercetin 4’-O-β-glucoside (3) from A. cepa as the inhibitors of melanin formation in B16 melanoma cells with IC₅₀ values of 26.5 and 131 μM, respectively. In addition, we evaluated the effect of some quercetin derivatives, such as isoquercitrin (2), quercetin 3,4’-O-diglucoside (4), rutin (5) and hyperin (6) on B16 melanoma cells. These quercetin derivatives did not show any inhibition of melanin formation. Furthermore, the ORAC values of compounds 1–6 were 7.64, 8.65, 4.82, 4.32, 8.17 and 9.34 μmol trolox equivalents/μmol, respectively. Dried skin of red onion showed inhibitory activity against melanin formation in B16 melanoma cells, as well as antioxidant properties.     

芦丁抑制牛血清白蛋白糖基化

目的：考察芦丁对糖及活性二羰基化合物诱导的牛血清白蛋白（bovine serum albumin,BSA）糖基化的抑制效果。方法：建立牛血清白蛋白-丙酮醛（bovine serum albumin-methylglyoxal,BSA-MGO）、牛血清白蛋白-乙二醛（bovine serum albumin-glyoxal,BSA-GO）、牛血清白蛋白-还原糖反应体系,利用荧光光谱的方法考察MGO、GO和还原糖对于BSA糖基化的影响,并考察芦丁对于3 个反应体系中晚期糖基化终末产物（advancedglycation end products,AGEs）的抑制作用。结果：MGO、GO、还原糖浓度分别为0.5、0.5、10 mmol/L时引发BSA蛋白糖基化反应较为显著。对于上述3 个体系,芦丁的添加浓度分别为0.25、0.25、1 mmol/L时,能有效地抑制AGEs的形成。结论：芦丁能有效地抑制BSA-MGO、BSA-GO、BSA-还原糖体系的牛血清白蛋白糖基化。     

Protective actions of microalgae against endogenous and exogenous advanced glycation endproducts (AGEs) in human retinal pigment epithelial cells

The formation and accumulation of advanced glycation endproducts (AGEs) is a key pathophysiological process involved in various diabetic complications such as diabetic retinopathy. In the present study, for the first time, protective effects of three microalgal strains, including their extracts and active compounds, against both endogenous and exogenous AGEs in cell-based models were investigated. Results showed that in cultured human-derived retinal pigment epithelial ARPE-19 cells, the extract of Chlorella zofingiensis and its nutritional ingredient astaxanthin exhibited significant inhibitory effects on the formation of endogenous N(ε)-carboxymethyllysine (CML), a key AGE representative, through the suppression of intracellular oxidative stress. On the other hand, extracts of Chlorella zofingiensis, Chlorella protothecoides and Nitzschia laevis as well as their nutritional ingredients, namely astaxanthin, lutein and eicosapentaenoic acid (EPA), attenuated the deleterious effects induced by exogenous AGEs, such as cell proliferation and mRNA upregulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2, which are critical steps involved in the pathogenesis of diabetic retinopathy. These results suggested the positive roles of astaxanthin, lutein and EPA in controlling the development of diabetes. These microalgae, therefore, might be regarded as beneficial foods and preventive agent choices for patients with diabetic retinopathy.     

Hepatoprotective and antioxidant activity of ethanolic extracts of edible lotus (Nelumbo nucifera Gaertn.) leaves

Lotus (Nelumbo nucifera Gaertn.), an aquatic vegetable, is extensively cultivated in eastern Asia, particularly in China. An ethanolic extract of the leaves was studied for its hepatoprotective activity against CCl₄-induced liver toxicity in rats. In vitro and in vivo antioxidant activity was also assessed. The results showed the hepatoprotective activity of lotus leaf extract (LLE) at doses of 300 and 500 mg/kg and in vivo antioxidant activity at 100 mg/kg that was comparable with that of a standard treatment comprising 100 mg/kg of silymarin, a known hepatoprotective drug. These data were supplemented with histopathological studies of rat liver sections. The main flavonoids and phenolic compounds of LLE were analysed by HPLC-DAD-ESI/MS methods. Six of the compounds detected were tentatively characterised, one as catechin glycoside and five as flavonoid glycoside derivatives: miricitrin-3-O-glucoside, hyperin, isoquercitrin, quercetin-3-O-rhamnoside and astragalin.     

不饱和脂肪酸对卵清蛋白糖基化反应的影响

糖基化反应是高营养食品常见的一类反应,食品中的脂类成分对糖基化反应有很大影响。本研究以葡萄糖和卵清蛋白（OVA）建立糖基化对照体系,与含有不饱和脂肪酸（UFA）的模型组进行对比,探究脂肪酸氧化对于糖基化反应产物二羰基化合物、晚期糖基化终产物（AGEs）及糖基化蛋白结构的影响。结果表明UFA通过不同方式促进二羰基化合物的形成,并通过改变OVA蛋白的高级结构显著促进糖基化反应。脂肪酸的不饱和度与二羰基化合物含量、TBA值、POV值均成正比,与羧甲基赖氨酸和吡咯素含量成反比。通过SEM结构模型的路径分析可知,脂质氧化次级产物对二羰基化合物的影响力较强（路径系数0.814）,对两种AGEs的影响力相对较弱（0.246）;脂质氧化初级产物对两种AGEs的影响力强于二羰基化合物。     

植物提取物对晚期糖基化终产物抑制机理的研究进展

晚期糖基化终产物（advanced glycation end products,AGEs）是由还原糖中的羰基与蛋白质、脂类和核酸中的游离氨基反应所形成的一类物质的总称,目前已证实该类物质具有一定的致病性,会导致神经退行性疾病、炎症反应、心脑血管疾病、糖尿病和癌症等疾病。本文旨在概述AGEs的来源、形成途径以及对人体的致病性,并重点介绍了植物提取物对于AGEs抑制机理的研究现状,为控制食品加工过程中产生的AGEs提供理论依据。